Development of cebranopadol, a potent dual MOP/NOP agonist, for the treatment of Opioid Use Disorder (OUD)

开发cebranopadol,一种有效的双重MOP/NOP激动剂,用于治疗阿片类药物使用障碍(OUD)

基本信息

  • 批准号:
    10759100
  • 负责人:
  • 金额:
    $ 332.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-15 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT/SUMMARY The U.S. is experiencing a crisis of opioid misuse, addiction, and overdose; in the most recent year, there were over 100,000 drug-related overdose deaths, 75% of which involved opioids. Current pharmacotherapies for opioid use disorder (OUD) target mu opioid peptide (MOP) receptors, one of five classes of opioid receptors. These therapies include the full MOP agonist methadone, the partial MOP agonist buprenorphine, and the MOP antagonist naltrexone. There are several drawbacks in using these medications to treat OUD, which include the potential for abuse, development of physical dependence, and risk of overdose, particularly for methadone and buprenorphine. Buprenorphine and naltrexone also trigger severe withdrawal symptoms. There is thus an urgent need for an improved therapeutic for the treatment of OUD. Cebranopadol (TRN-228) is a first-in-class synthetic drug developed for its dual-action mechanism in treating pain, mediated by high affinity and potency for both MOP and nociceptin/orphanin FQ receptor (NOP). NOP receptor activation has been associated with reduced development of tolerance, abuse-related behavior, addiction, and physical dependence. In this UG3/UH3 proposal, Park Therapeutics is developing TRN-228 as a first-in-class dual MOP/NOP agonist that can be used as a safe and effective treatment for OUD. Preliminary nonclinical and clinical data indicate that cebranopadol has low potential for abuse and physical dependence and produces milder respiratory depression compared to pure MOP agonists such as morphine and oxycodone. TRN-228 also decreases morphine, heroin, and cocaine self-administration in rats and did not induce withdrawal when given to opioid-dependent rats. The UG3 phase of this proposal will test whether oral TRN-228 is a safe and potentially effective alternative treatment for OUD, based on the following Specific Aims: 1) determining the effects of TRN-228 on intravenous fentanyl self-administration and fentanyl-induced respiratory depression in opioid-dependent rats, 2) determining the IV abuse potential of TRN-228, and 3) assessing the ability of TRN-228 to suppress withdrawal. Upon meeting the UG3 Go/No-Go milestones, Park will progress to the UH3 phase which will demonstrate the therapeutic efficacy of TRN-228 in decreasing opioid use with low risk of withdrawal or abuse, which will be accomplished by 4) determining the effects of TRN-228 on fentanyl-induced respiratory depression in opioid-tolerant participants and 5) evaluating the ability of TRN-228 to block the subjective effects of hydromorphone. These studies will significantly advance the field by establishing the safety and preliminary efficacy of TRN-228. Successful completion of these aims will guide future efforts to establish a clinical program for FDA approval.
抽象/总结

项目成果

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Mark K Greenwald其他文献

Mark K Greenwald的其他文献

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{{ truncateString('Mark K Greenwald', 18)}}的其他基金

Planning a Multi-Level Intervention to Reduce Substance Use Stigma in HIV Prevention and Care
规划多层次干预措施以减少艾滋病毒预防和护理中的药物使用耻辱
  • 批准号:
    10669764
  • 财政年份:
    2021
  • 资助金额:
    $ 332.96万
  • 项目类别:
Behavioral Economic Analysis of Medical Marijuana Use in HIV+ Patients
HIV 患者使用医用大麻的行为经济学分析
  • 批准号:
    8331559
  • 财政年份:
    2011
  • 资助金额:
    $ 332.96万
  • 项目类别:
Behavioral Economic Analysis of Medical Marijuana Use in HIV+ Patients
HIV 患者使用医用大麻的行为经济学分析
  • 批准号:
    8484810
  • 财政年份:
    2011
  • 资助金额:
    $ 332.96万
  • 项目类别:
Behavioral Economic Analysis of Medical Marijuana Use in HIV+ Patients
HIV 患者使用医用大麻的行为经济学分析
  • 批准号:
    8228758
  • 财政年份:
    2011
  • 资助金额:
    $ 332.96万
  • 项目类别:
Human Laboratory Model of Cocaine Treatment: Behavioral Economic Analysis
可卡因治疗的人体实验室模型:行为经济学分析
  • 批准号:
    7894996
  • 财政年份:
    2009
  • 资助金额:
    $ 332.96万
  • 项目类别:
Human Laboratory Model of Cocaine Treatment: Behavioral Economic Analysis
可卡因治疗的人体实验室模型:行为经济学分析
  • 批准号:
    7697838
  • 财政年份:
    2009
  • 资助金额:
    $ 332.96万
  • 项目类别:
Development and Use of rtfMRI for Self-control of Nicotine Craving
rtfMRI 的开发和使用用于自我控制尼古丁渴望
  • 批准号:
    7588461
  • 财政年份:
    2008
  • 资助金额:
    $ 332.96万
  • 项目类别:
Development and Use of rtfMRI for Self-control of Nicotine Craving
rtfMRI 的开发和使用用于自我控制尼古丁渴望
  • 批准号:
    8087596
  • 财政年份:
    2008
  • 资助金额:
    $ 332.96万
  • 项目类别:
Development and Use of rtfMRI for Self-control of Nicotine Craving
rtfMRI 的开发和使用用于自我控制尼古丁渴望
  • 批准号:
    8104244
  • 财政年份:
    2008
  • 资助金额:
    $ 332.96万
  • 项目类别:
Development and Use of rtfMRI for Self-control of Nicotine Craving
rtfMRI 的开发和使用用于自我控制尼古丁渴望
  • 批准号:
    8282904
  • 财政年份:
    2008
  • 资助金额:
    $ 332.96万
  • 项目类别:

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